Variant 2-31580605-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000622030.2(SRD5A2):c.281+15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,523,552 control chromosomes in the GnomAD database, including 360,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36117 hom., cov: 37)

Exomes 𝑓: 0.69 ( 324066 hom. )

Consequence

SRD5A2
ENST00000622030.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.140

Variant links:

Genes affected

SRD5A2 (HGNC:11285): (steroid 5 alpha-reductase 2) This gene encodes a microsomal protein expressed at high levels in androgen-sensitive tissues such as the prostate. The encoded protein is active at acidic pH and is sensitive to the 4-azasteroid inhibitor finasteride. Deficiencies in this gene can result in male pseudohermaphroditism, specifically pseudovaginal perineoscrotal hypospadias (PPSH). [provided by RefSeq, Jul 2008]

SRD5A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-31580605-A-G is Benign according to our data. Variant chr2-31580605-A-G is described in ClinVar as [Benign]. Clinvar id is 97403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A2	NM_000348.4 linkuse as main transcript	c.281+15T>C		intron_variant		ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533072.3 linkuse as main transcript	c.27-46839T>C		intron_variant			XP_011531374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A2	ENST00000622030.2 linkuse as main transcript	c.281+15T>C		intron_variant		1	NM_000348.4	ENSP00000477587	P1

Frequencies

GnomAD3 genomes

AF:

0.687

AC:

104499

AN:

152126

Hom.:

36099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.704

Gnomad AMI

AF:

0.729

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.765

Gnomad EAS

AF:

0.475

Gnomad SAS

AF:

0.617

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.696

Gnomad OTH

AF:

0.699

GnomAD3 exomes

AF:

0.646

AC:

97512

AN:

150880

Hom.:

32064

AF XY:

0.647

AC XY:

52163

AN XY:

80626

show subpopulations

Gnomad AFR exome

AF:

0.698

Gnomad AMR exome

AF:

0.616

Gnomad ASJ exome

AF:

0.766

Gnomad EAS exome

AF:

0.442

Gnomad SAS exome

AF:

0.616

Gnomad FIN exome

AF:

0.671

Gnomad NFE exome

AF:

0.680

Gnomad OTH exome

AF:

0.677

GnomAD4 exome

AF:

0.686

AC:

940620

AN:

1371308

Hom.:

324066

Cov.:

AF XY:

0.684

AC XY:

460572

AN XY:

673526

show subpopulations

Gnomad4 AFR exome

AF:

0.710

Gnomad4 AMR exome

AF:

0.623

Gnomad4 ASJ exome

AF:

0.765

Gnomad4 EAS exome

AF:

0.512

Gnomad4 SAS exome

AF:

0.629

Gnomad4 FIN exome

AF:

0.674

Gnomad4 NFE exome

AF:

0.696

Gnomad4 OTH exome

AF:

0.689

GnomAD4 genome

AF:

0.687

AC:

104562

AN:

152244

Hom.:

36117

Cov.:

AF XY:

0.686

AC XY:

51054

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.704

Gnomad4 AMR

AF:

0.669

Gnomad4 ASJ

AF:

0.765

Gnomad4 EAS

AF:

0.475

Gnomad4 SAS

AF:

0.617

Gnomad4 FIN

AF:

0.689

Gnomad4 NFE

AF:

0.696

Gnomad4 OTH

AF:

0.696

Alfa

AF:

0.693

Hom.:

40034

Bravo

AF:

0.684

Asia WGS

AF:

0.515

AC:

1793

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not provided

Benign:1Other:1

not provided, no classification provided	literature only	University of Sydney Medical Foundation	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.6

DANN

Benign

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over